There are approximately four million cases of Chlamydia trachomatis diagnosed annually in the US. Most of these cases are diagnosed by techniques that require invasive sample collection (endocervical or urethral samples) and hours to perform the required testing. For the screening and successful treatment of large populations this scenario has three problems: 1) collection techniques may cause patient discomfort and instill reluctance in the prospective patient, 2) specialized examination rooms for female patients are required and 3) the recall of patients for treatment after receipt of test results is often unsuccessful. There is evidence that in populations served by public health that a significant number of infected individuals never receive treatment due to an unwillingness to return to the clinic and that even when treated, multi- day treatments have a significant lack of compliance. Single dose treatments are now available with essentially 100% cure rates. The Chlamydia Optical ImmunoAssay (OIA[TM]) has been shown to have a sensitivity in detecting chlamydia from endocervical samples equal to that of more complex tests. Additionally, OIA specificity is 100% as compared to PCR confirmed results; important when considering a test for screening low incidence populations. In that the OIA is a 24 minute test, results can be generated while the patient is still in the clinic. Having the OIA result and the patient available would allow the clinician to use single dose treatment thus negating the need for patient call back and concern for antibiotic course compliance. It is the objective of this proposal to expand the performance of OIA such that less invasive sample types can be used and hence positively impact the effective diagnosis and treatment of chlamydia infections. The research is proposed as follows: 1. The proposed expanded sample types, including female and male urine and self-sample vaginal swabs, would be tested using the current OIA to establish performance characteristics. OIA results from this initial study would be compared to a standard such as cell culture and to a currently available rapid (<30 minutes) chlamydia test. 2. Improved sample processing for urine will be investigated. Elimination of procedures such as centrifugation by concentration of potential free chlamydia lipolysaccharide (LPS) by adsorptive or biochemical means will be explored. Improved extraction techniques, specifically centering on organic partitioning will be explored. 3. New anti-LPS monoclonal antibodies complimentary to the currently used monoclonal will be tested. A "cocktail" of reagents may amplify the OIA and thus increase sensitivity. Alternative substrates, LPS capture methods and signal generating techniques will also be examined to not only increase assay sensitivity, but also potentially shorten assay time from the current 24 minutes. 4. Finally, the enhanced OIA will be tested in sample populations to assess improved assay performance.